mtDB:Human Mitochondrial Genome Databa,
a resource for population genetics and
medical sciences
Max Ingman 1,2,*and Ulf Gyllensten 2
1Centre for Integrative Genomics,University of Lausanne,Switzerland and 2Department of Genetics and Pathology,Rudbeck Laboratory,University of Uppsala,Uppsala,Sweden
Received August 9,2005;Revid and Accepted September 12,2005
ABSTRACT The mitochondrial genome,contained in the subcel-lular mitochondrial network,encodes a small number of peptides pivotal for cellular energy production.Mitochondrial genes are highly polymorphic and cata-loguing existing variation is of interest for medical scientists involved in the identification of mutations causing mitochondrial dysfunction,as well as for population genetics studies.Human Mitochondrial Genome Databa (mtDB)(pat.uu./mtDB)has provided a comprehensive databa of complete human mitochondrial genomes since early 2000.At this time,owing to an increa in the number of published complete human mitochondrial genome quenc
es,it became necessary to provide a web-bad databa of human whole genome and complete coding region quences.As of August 2005this databa contains 2104quences (1544complete genome and 560coding region)available to download or arch for specific polymorphisms.Of special interest to medical rearchers and popu-lation geneticists evaluating specific positions is a complete list of (currently 3311)mitochondrial poly-morphisms among the quences.Recent expan-sions in the capabilities of mtDB include a haplotype arch function and the ability to identify and download quences carrying particular variants.INTRODUCTION The mitochondrial genome supplies parts of the protein machinery that are necessary for oxidative phosphorylation (OXPHOS),by utilizing a ries of five multiple-subunit enzymes located within the mitochondrial inner membrane.The complex constituents are encoded by both nuclear and mitochondrial genes.A genetic defect could therefore be due to mutations in genes of either system.Since new mutations are introduced more frequently to the mitochondrial genome,a higher proportion of mitochondrial dysfunction is due to mitochondrial DNA (mtDNA)mutations.A number of human
dias have been shown to be caud by mitochondrial muta-
tions,such as Leber’s hereditary optic neuropathy (LHON)(1)and neurogenetic muscle weakness,ataxia,and retinitis pigmentosa (NARP)(2).In the evaluation of a possible func-tional effect
of a mitochondrial variant found in a group of patients,reliable population frequency data for the variant under study is needed.The Human Mitochondrial Genome Databa (mtDB)provides such a compilation of available genome quences information for this purpo.
The mtDNA of most metazoan species (including humans)is predominantly maternally inherited (3).This clonal inher-itance coupled with a substitution rate that in vertebrates is
typically 5to 10times that of nuclear DNA (4)has made
mitochondria an attractive source of DNA polymorphism data for population genetics studies in a wide range of species.The lack of recombination among maternal and paternal mito-chondrial genomes allows the tracing of a direct genetic line where all polymorphism is due to mutation and the high sub-stitution rate makes it possible to study variation between cloly related individuals (i.e.within species).mtDNA quences have been the main tool in a large number of studies of human evolution.The Human Mitochondrial Genome Data-ba (mtDB)is a repository for the quences and will pro-
vide scientists with access to a common resource for future
studies in this field.
Since 2000,with the publication of the first comprehensive
study on complete human mitochondrial genome quences
(5),the amount of data available from mitochondrial genomes
has been growing rapidly.However,polymorphism infor-mation from the data is becoming more time consuming to produce.The mtDB provides a unique resource to both medical and human population genetic rearchers.Here,*To whom correspondence should be addresd.Tel:+41216923962;Fax:+46184714931;Email:max.ingman@unil.ch
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ÓThe Author 2006.Published by Oxford University Press.All rights rerved.
The online version of this article has been published under an open access model.Urs are entitled to u,reproduce,disminate,or display the open access version of this article for non-commercial purpos provided that:the original authorship is properly and fully attributed;the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given;if an article is subquently reproduced or disminated not in its entirety but only in part or as a derivative work this must be clearly indicated.For commercial re-u,plea contact journals.permi
ssions@oxfordjournals Nucleic Acids Rearch,2006,Vol.34,Databa issue D749–D751
doi:10.1093/nar/gkj010
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published mitochondrial genome quences are collected from GenBank and other sources (not all quences are submitted to GenBank)and made available for download.In addition,extensive polymorphism information from the complete datat is easily accessible.Databa content The mtDB databa contains three principal types of content for rearchers:(i)Download of all mitochondrial quences either as indi-viduals or population ts.The quences are grouped into 10major geographic regions bad on the population
origin of the donor (Table 1).In cas where the geo-graphic origin of the donor is different from their suppod
historical background,the quences are listed under the heading that best fits their donors’ancestry.For example,
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African American,European American and Asian American quences are not listed under North America but under the headings Africa,Europe and Asia,respec-tively.Large ts from the same population are available as batches of individual files.All quences are cross-referenced to their original publications and to GenBank accession numbers,where available.There are currently 2104mitochondrial quences at mtDB.(ii)A list of all variable positions [numbered as in Cambridge Reference Sequence,CRS (6)]among complete,or near complete,mitochondrial quences (Figure 1).Currently,3311polymorphic sites are identified and characterized in tabulated form.This table compris a parate line for each variable site with a count of how many quences contain each particular nucleotide variant at that site,the genic location of that site,the codon number and posi-tion and details of amino acid changes.An interested rearcher can click on the number of a particular variant to obtain a list of all quences that contain that parti-cular variant.The quences can then be downloaded from the list.All inrtions relative to CRS have been removed.
变作文(iii)A arch function for mitochondrial haplotypes.This goes a step beyond the list of variable positions in that quences carrying specific haplotypes can be retrieved by entering the position and nucleotide for up to 10loci.Only quences that match all the criteria will be returned.Again,the quences can then be downloaded from the databa.
Some population genetics rearchers u predefined hap-
lotypes (haplogroups)purported to designate specific mito-chondrial lineages.As a compliment to our arch function,this page has a link to a haplogroup tree where clicking the
individual haplogroup letters will return a list of all quences that belong to that particular group.
Table 1.Summary table of the number of quences from each of the 10geo-数码相机维修
graphic regions Population Complete Coding region Africa
American 56Other 58
America (North)6
America (South)3
Asia
Japane 672
Chine 48
American 69
Other 70
Australia
Aborigine 20
Europe 535American 241435
Finnish 192
Italian 62
Other 40
Melanesia
New Guinea 21
Other 2
Middle East 7
Polynesia 6
South Asia
Indian 75Other 21
Total:1544560
relative to CRS (6).
Population groups for which a large number of quences are available are
indicated parately.Coding region quences extend from np 577to
16023,
Figure 1.Truncated table of polymorphic sites.Each row of the table shows nucleotide position [relative to Anderson (Cambridge Reference Sequence,CRS)(6)],CRS nucleotide state at that position,the number of databa quences with A,G,C,T or gap,and the functional region that the site is in.If the functional region is a protein coding gene,also listed is the codon number,the codon position,the amino acid state in CRS and for the variant,whether the change is synonymous or not.Clicking the number of quences with a particular nucleotide state will retrieve a list of all quences that carry that particular variant.D750Nucleic Acids Rearch,2006,Vol.34,Databa issue
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Databa interface
To facilitate easy updating of mtDB,all data pages are pro-duced dynamically by PHP scripts.PHP is an easy-to-u scripting language that integrates well with HTML.Data is pard on the rver machi
ne and an HTML output is nt to the client.This is independent of the client’s operating system, browr and installed options.The only exception to this,is the polymorphic sites,nucleotide variants and amino acid states list which is produced by a parate script and the HTML output saved to avoid long processing time for individual requests.The core databa is a textfile of aligned quences. New quences can be simply pasted to this list and are then included in arches.
CONCLUSIONS
mtDB is the only comprehensive online source for the data contained within it.This includes the quences themlves as many have not been deposited in a publicly available databa such as GenBank.The list of mitochondrial polymorphisms continually grows with the addition of new quences and is an important resource for phylogenetic and medical studies.The ability to arch for multiple-variant haplotypes adds further detail to the latent data.We are committed to the maintenance of this databa and hope that it will be a uful resource for rearchers for years to come.
ACKNOWLEDGEMENTS
This rearch has been supported by the Swedish National Rearch Council(UG).Funding to pay th
e Open Access publication charges for this article was provided by Swedish National Rearch Council(UG).
Conflict of interest statement.None declared.
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